The Sickening Mind: Brain, Behaviour, Immunity and Disease. Paul Martin

of thing.

      Despite their appearance of objectivity and precision, immunological measures are not totally reliable and, to a degree, depend upon subjective judgements. Conversely, the common prejudice that all psychological measures are by definition subjective, unreliable and woolly is a gross fallacy. Some are, but others are not. Experimental psychologists and behavioural biologists have been devising valid, reliable ways of measuring behaviour, psychological states and emotions for over half a century.⁹ Psychological measures are not always perfect, but they are inherently no better or worse than immunological measures in terms of their reliability, validity and objectivity. (Here endeth the lesson.)

The mind – immunity connections

      Scientists and doctors have traditionally tended to regard the immune system as an autonomous entity that operates to a large degree independently of the mind and behaviour; an exquisite piece of biological machinery honed by millions of years of evolution to act autonomously in protecting the body from anything the outside world can throw at it. But this view is now known to be fundamentally wrong.

      The body’s three main regulatory systems – the central nervous system (which includes the brain), the endocrine system (which produces hormones) and the immune system – do not work in isolation from one another. On the contrary, they are intimately connected and interact with each other in many important ways. Events occurring in the brain can produce changes within the endocrine and immune systems through a variety of routes, including specialized nerve pathways and chemical messengers. The effect may be to impair or enhance aspects of immune function, with potential consequences for health. The central nervous system, immune system and endocrine system are part of an integrated regulatory network that helps to ensure the survival and effective functioning of the whole organism. We are not just a bag of bits.

      Another common misconception is that organisms work in a top-down, hierarchical manner with commands flowing in a single direction, from the brain to the rest of the body. In reality, information flows both ways along the various biological pathways that connect the central nervous system, endocrine system and immune system. Activity within the immune system can therefore influence the brain, mental state and behaviour.

      Some scientists have likened the immune system to a sort of sensory organ, which is distributed throughout the body and provides the brain and endocrine system with information about the internal and external environment. This analogy makes good biological sense. The immune system detects the presence of antigens, including cells of its own body which have undergone change. It then transmits this information to the central nervous system, together with information about its immune response.

      The new field of scientific research which is concerned with the complex inter-relationships between psychological and emotional factors, the brain, hormones, immunity and disease goes by the jaw-bending name of psychoneuroimmunology. In the next chapter we shall examine a few examples of how the brain and immune system interact. Before we do that, however, let us glance at the nature of the mechanisms which connect the brain and the immune system.

      Since the 1980s, psychoneuroimmunologists have made considerable progress in understanding the biological pathways by which the brain and immune system influence each other. These pathways are of two basic sorts: electrical pathways using nerve connections, and chemical pathways using hormones, neuropeptides and other chemical messenger molecules. The specialized nature of these mechanisms strongly implies that they have evolved for a purpose – to enable the brain and the immune system to communicate with each other.

      One good reason for believing that the brain and the immune system are meant to communicate is that they are hard-wired to each other by nerve connections. The tissues of the immune system are connected to the central nervous system by a rich supply of nerves. These nerve connections are responsible, amongst other things, for helping to regulate the development, activity and movement of lymphocytes and other immune cells.

      Immune tissues in the spleen, bone marrow, thymus, lymph nodes, tonsils and gut are all abundantly supplied with nerve endings. Bone marrow, for example, is connected to the central nervous system by nerves emanating from the spinal nerve which supplies that region of the body. Some of the nerve connections in immune tissues do have other purposes, such as helping to regulate the local flow of blood, but some nerves undoubtedly pass information between the immune tissues and the brain. The spleen has a dense network of nerve connections and at least half of them are involved in transmitting information to and from the brain.

      The second principal way in which the brain and immune system communicate is through an array of special chemical messenger molecules. The central nervous system and the immune system – the body’s two great regulatory and memory systems – have a lot of chemical communications hardware (or should I say wetware) in common. That such vast numbers of these chemical messengers have been discovered indicates their importance as a mechanism of communication between the central nervous system and the immune system, and also within each system.

      Neurotransmitters, hormones and other chemical messenger molecules that were once thought to be restricted to the brain and nervous system are now known to be active within the immune system as well. Conversely, certain immunotransmitters and other chemical messengers that were once thought to be exclusive to the immune system are now known to act on the endocrine and central nervous systems. The brain and the immune system speak the same languages.

      Cells of the immune system have special biochemical receptor sites on their surfaces which respond specifically to chemical messengers produced by the central nervous system. Lymphocytes and other immune cells respond to a range of neuropeptides, neurotransmitters and hormones which are either produced directly by the central nervous system, or whose secretion is under its control. These chemical messengers include noradrenaline, corticosteroid hormones, endorphins, encephalins, growth hormone, adrenocorticotrophic hormone (ACTH), prolactin, substance P, substance K, vasoactive intestinal peptide (VIP), angiotensin and somatostatin. A number of these chemical messengers travel to the immune system via the blood circulation; others, like neuropeptides, are also delivered locally from nerve endings.

      These chemical messengers are able to modulate aspects of cell-mediated and antibody-mediated immunity. For example, the hormone noradrenaline, which is released from the adrenal glands (under stimulation from the brain) and from nerve endings, has widespread effects on immune function. Noradrenaline can facilitate the production of antibodies in various immune tissues; it can also inhibit the division of lymphocytes and impede the destruction of virus-infected cells or cancer cells by the immune system. Another messenger molecule, substance P, makes lymphocytes more responsive to stimulation, increases the production of certain types of antibody and facilitates the movement of lymphocytes to sites of infection.

      We shall see in chapter 5 how psychological stress stimulates the release of hormones, including cortisol, a steroid hormone which suppresses various aspects of immune activity. The stress-induced release of cortisol is controlled by a region of the brain called the hypothalamus. The hormone prolactin is also released in response to psychological stress; unlike cortisol, however, its main effect on immune activity is stimulative.

      Chemical communication between the central nervous system and immune system also works both ways. The immune system sends chemical messages to the brain. Immune cells produce neuropeptides, hormones and other chemical messengers, including ACTH, endorphins, encephalins, VIP and growth hormone, which influence both the endocrine and central nervous systems.

      Some of the most important messenger molecules mediating the communication between the central nervous system and immune system are the cytokines. These were originally thought to be exclusive to the immune system, but they are now known to act on the central nervous system and endocrine system as well. Scientists have found that cells in several regions of the brain and central nervous system either contain cytokines or have receptor sites for them. When cytokines are released by activated immune cells they can have widespread effects on an organism’s nerves, hormone levels and psychological state.